Experimental Study On Effects Of Penehyclidine Hydrochloride On Expressions Of NF-κB And TNF-αin Brains Of Rats After Acute Global Cerebral Ischemia/Reperfusion

Objective: To observe the effects of Penehyclidine Hydrochloride on expressions of NF-κB and TNF-αin brains of rats after acute global cerebral ischemia/reperfusion, and to compare with which of Anisodamine, to study the effects of Penehyclidine Hydrochloride on acute global cerebral ischemia/reperfusion injury and the mechanism.Method: Divide healthy Sprage-Dawley rats into four groups randomly: group S (sham operation group, n=24), group IR (ischemia/reperfusion , n=24), group A (Anisodamine treated group , n=24), group P (Penehyclidine Hydrochloride treated group,n=24),and divide every group into four subsets by reperfusion time: 2h, 6h, 12h, 24h. The model of global cerebral ischemia and reperfusion was established by Pulsinelli's method,and the ischemia time was 10min. Penehyclidine Hydrochloride and Anisodamine were administrated by intraperitoneal injection respectively in group P and group A just before reperfusion, as the same volume of Sodium Chloride was administrated in group IR. All the rats which the model was successful must be treated with perfusion fixation via heart, and be decapitated and take the brain tissue of 2.5mm thickness starting from the setpoint which is 2.5mm to the antinion, which was made into paraffin section, to examine the expression of NF-κB by immunohistochemical method, the rest brain tissue was kept in freezer of -70℃after quick freezing by liquid nitrogen, to examine the expression of TNF-αby ELISA after homogenate,the deformation of nurons was observed through optic microscope after HE staining.Results:①Compared with group S, the expressions of NF-κB and TNF-αin group IR increased significantly and have significant otherness ,P<0.01.②Compared with group IR, the expressions of NF-κB in group A and P decreased significantly and have significant otherness ,P<0.05 or P<0.01; the expressions of TNF-αin group A and P decreased significantly , too, and have significant otherness except in 2h subset, P<0.05 or P<0.01.③Compared with group A, the expressions of NF-κB in group P of 6h and 12h subsets decreased significantly and have significant otherness ,P<0.05 ; the expressions of TNF-αin group P of 12h and 24h subsets decreased significantly and have significant otherness ,P<0.05 or P<0.01.④Compared with group S, nerve cells in group IR were damaged severely, and with the time of reperfusion prolonged, the number of abnormal nerve cells was gradually increased,as well as the number of normal was gradually decreased; Compared with group IR, nerve cells in group A and P were damaged much slightly, and the damage in group P was most slightly in all the four groups except group S.Conclusions:①Expressions of NF-κB and TNF-αin brains of rats increased significantly after acute global cerebral ischemia/reperfusion;②Penehyclidine Hydrochloride can have more significant inhibitory action on the expressions of NF-κB and TNF-αin brains of rats increased significantly after acute global cerebral ischemia/reperfusion, campared with Anisodamine;③Penehyclidine Hydrochloride can ease the acute global cerebral ischemia/reperfusion injury to protect brain tissues by inhibiting the expressions of NF-κB and TNF-αin brains of rats.